Background: Pityriasis (tinea) versicolor is a superficial fungal infection of the stratum corneum caused by Malassezia species. The diagnosis is made clinically by its classic appearance of round or oval macules with fine scale that may be hyperpigmented or hypopigmented. Diagnosis may also be confirmed with microscopic evaluation of skin scrapings that reveal both short, stubby hyphae, and spores under KOH preparation. Ketoconazole is an important treatment of pityriasis versicolor but is primarily used in cream formulas. A foam vehicle has been shown to improve drug absorption through the stratum corneum and distribution in the skin. This study has assessed the safety and efficacy of ketoconazole 2% foam in treatment of pityriasis versicolor. Methods: Ketoconazole 2% foam was evaluated in a single-center, open-label, one-arm pilot study which enrolled eleven subjects to gain 10 evaluable subjects aged 21 years and older with a clinical diagnosis of tinea versicolor and positive KOH using calcofluor. The subjects came for 4 scheduled visits (baseline, week 1, week 2, and week 4) and were instructed to apply ketoconazole 2% foam to all affected areas twice daily for 2 weeks. At each visit, mycological and clinical assessment of a target area was done, along with static global assessment and body surface area estimation of the disease in each subject. Patient questionnaires were given at baseline and at week 2 to rate pruritus and satisfaction with the foam. Results: At the week 2 visit, following the treatment period, three out of ten evaluable subjects had negative skin samples prepared with KOH/calcifluor. Of these three, one subject later showed recurrence of fungal elements consistent with tinea versicolor at the week 4 follow-up visit. The other negative subjects remained negative and four additional subjects tested negative at week 4. Three subjects with positive samples at week 4 had only yeast forms without hyphae present. Investigator ratings of the target area were averaged for each clinical feature and demonstrated improvement in scale, hyper- or hypopigmentation, erythema, and induration throughout the study. Average pruritus score increased slightly 1 week after the baseline visit, but then improved steadily over the remaining visits. The investigator's static global assessment rating showed improvement from mild to moderate disease at baseline to minimal or no disease at week 4 in 7 subjects. The remaining subjects showed neither improvement nor progression of the disease throughout the study. One out of the eleven subjects enrolled did not complete the study. One subject noted mild skin burning sensation after application of medicine. Post-treatment patient questionnaires indicated overall satisfaction with the foam vehicle. Limitations: This was a single-arm, open-label, noncomparative trial. Conclusion: Ketoconazole 2% foam improved overall clinical assessment and microscopic evidence of pityriasis versicolor in all subjects with favorable patient feedback regarding the novel foam vehicle. Copyright © 2014 Journal of Drugs in Dermatology.